(Circulation. 1996;94:2057-2063.)
© 1996 American Heart Association, Inc.
Articles |
Fibrinolytic Factors and the Risk of Myocardial Infarction or Sudden Death in Patients With Angina Pectoris
the Hematology Laboratory, CHU Timone, Marseille, France (I.J.-V., M.C.A.); the Medical Statistics Unit, London (UK) School of Hygiene and Tropical Medicine (S.D.M.P., S.G.T.); Centralsygehuset, Esbjerg, Denmark (J.J.); and Gaubius Laboratory, TNO-PG, Leiden, Netherlands (F.H.).
Correspondence to Irene Juhan-Vague, Hematology Laboratory, CHU Timone, 13385 Marseille Cedex 5, France.
Background Disturbances of the fibrinolytic system that lead to decreased removal of fibrin deposits may be important risk factors for coronary thrombosis. There is as yet no consensus on the prognostic value of fibrinolytic parameters, which may be attributed in part to the choice of confounding variables controlled for.
Methods and Results The ECAT study is a prospective multicenter study of 3043 patients with angina pectoris followed for 2 years. Baseline measurements included 10 fibrinolytic variables. The results were analyzed in relation to the subsequent incidence of myocardial infarction or sudden coronary death. They are presented before and after adjustment for clusters of confounding variables that are markers of different mechanisms: insulin resistance (body mass index, triglyceride, and HDL cholesterol), inflammation (fibrinogen and C-reactive protein), and endothelial cell damage (von Willebrand factor). An increased incidence of events was associated with higher baseline concentrations of tissue plasminogen activator (TPA) antigen (P=.0002), plasminogen activator inhibitor-1 (PAI-1) activity (P=.02), and PAI-1 antigen (P=.001). The associations of PAI-1 activity and PAI-1 antigen with risk of events disappeared after adjustment for parameters reflecting insulin resistance but were not affected by other adjustments. TPA antigen was affected to a similar extent by adjustment for parameters reflecting insulin resistance, inflammation, or endothelial cell damage, but the risk association disappeared only after combined adjustments.
Conclusions The prognostic role of PAI-1 in predicting coronary events is related principally to insulin resistance, whereas that of TPA antigen could be explained only by its relationship with different mechanisms, including insulin resistance, inflammation, and endothelial cell damage.
Key Words: risk factors • fibrinolysis • plasminogen activators • angina • myocardial infarction
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M. Borries, M. Heins, Y. Fischer, H. Stiegler, A. Peters, H. Reinauer, F. C. Schoebel, B. E. Strauer, and M. Leschke Changes of hemostasis, endogenous fibrinolysis, platelet activation and endothelins after percutaneous transluminal coronary angioplasty in patients with stable angina J. Am. Coll. Cardiol., August 1, 1999; 34(2): 486 - 493. [Abstract] [Full Text] [PDF]
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 G. W. de Valk-de Roo, C. D.A. Stehouwer, J. Lambert, C. G. Schalkwijk, M. J. van der Mooren, C. Kluft, and C. Netelenbos Plasma Homocysteine Is Weakly Correlated with Plasma Endothelin and von Willebrand Factor but not with Endothelium-dependent Vasodilatation in Healthy Postmenopausal Women Clin. Chem., August 1, 1999; 45(8): 1200 - 1205. [Abstract] [Full Text] [PDF]
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M. Cesari and G. P. Rossi Plasminogen Activator Inhibitor Type 1 in Ischemic Cardiomyopathy Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1378 - 1386. [Full Text] [PDF]
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A. Mavri, M. Stegnar, M. Krebs, J. T. Sentocnik, M. Geiger, and B. R. Binder Impact of Adipose Tissue on Plasma Plasminogen Activator Inhibitor-1 in Dieting Obese Women Arterioscler Thromb Vasc Biol, June 1, 1999; 19(6): 1582 - 1587. [Abstract] [Full Text] [PDF]
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B. A. Allison, L. Nilsson, F. Karpe, A. Hamsten, and P. Eriksson Effects of Native, Triglyceride-Enriched, and Oxidatively Modified LDL on Plasminogen Activator Inhibitor-1 Expression in Human Endothelial Cells Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1354 - 1360. [Abstract] [Full Text] [PDF]
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P. E. Morange, M. C. Alessi, M. Verdier, D. Casanova, G. Magalon, and I. Juhan-Vague PAI-1 Produced Ex Vivo by Human Adipose Tissue Is Relevant to PAI-1 Blood Level Arterioscler Thromb Vasc Biol, May 1, 1999; 19(5): 1361 - 1365. [Abstract] [Full Text] [PDF]
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D. E. Newby, R. A. Wright, C. Labinjoh, C. A. Ludlam, K. A. A. Fox, N. A. Boon, and D. J. Webb Endothelial Dysfunction, Impaired Endogenous Fibrinolysis, and Cigarette Smoking : A Mechanism for Arterial Thrombosis and Myocardial Infarction Circulation, March 23, 1999; 99(11): 1411 - 1415. [Abstract] [Full Text] [PDF]
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M. Cushman, R. N. Lemaitre, L. H. Kuller, B. M. Psaty, E. M. Macy, A. R. Sharrett, and R. P. Tracy Fibrinolytic Activation Markers Predict Myocardial Infarction in the Elderly : The Cardiovascular Health Study Arterioscler Thromb Vasc Biol, March 1, 1999; 19(3): 493 - 498. [Abstract] [Full Text] [PDF]
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M. Pahor, M. B. Elam, R. J. Garrison, S. B. Kritchevsky, and W. B. Applegate Emerging Noninvasive Biochemical Measures to Predict Cardiovascular Risk Arch Intern Med, February 8, 1999; 159(3): 237 - 245. [Abstract] [Full Text] [PDF]
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W. Koenig, M. Sund, M. Frohlich, H.-G. Fischer, H. Lowel, A. Doring, W. L. Hutchinson, and M. B. Pepys C-Reactive Protein, a Sensitive Marker of Inflammation, Predicts Future Risk of Coronary Heart Disease in Initially Healthy Middle-Aged Men : Results From the MONICA (Monitoring Trends and Determinants in Cardiovascular Disease) Augsburg Cohort Study, 1984 to 1992 Circulation, January 19, 1999; 99(2): 237 - 242. [Abstract] [Full Text] [PDF]
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A. M. Thogersen, J.-H. Jansson, K. Boman, T. K. Nilsson, L. Weinehall, F. Huhtasaari, and G. Hallmans High Plasminogen Activator Inhibitor and Tissue Plasminogen Activator Levels in Plasma Precede a First Acute Myocardial Infarction in Both Men and Women : Evidence for the Fibrinolytic System as an Independent Primary Risk Factor Circulation, November 24, 1998; 98(21): 2241 - 2247. [Abstract] [Full Text] [PDF]
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E. J. Giltay, J. M. H. Elbers, L. J. G. Gooren, J. J. Emeis, T. Kooistra, H. Asscheman, and C. D. A. Stehouwer Visceral Fat Accumulation Is an Important Determinant of PAI-1 Levels in Young, Nonobese Men and Women : Modulation by Cross-Sex Hormone Administration Arterioscler Thromb Vasc Biol, November 1, 1998; 18(11): 1716 - 1722. [Abstract] [Full Text] [PDF]
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B. Kristensen, J. Malm, T. K. Nilsson, J. Hultdin, B. Carlberg, and T. Olsson Increased Fibrinogen Levels and Acquired Hypofibrinolysis in Young Adults With Ischemic Stroke Stroke, November 1, 1998; 29(11): 2261 - 2267. [Abstract] [Full Text] [PDF]
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J. S. Pankow, A. R. Folsom, M. A. Province, D. C. Rao, R. R. Williams, J. Eckfeldt, and T. A. Sellers Segregation Analysis of Plasminogen Activator Inhibitor-1 and Fibrinogen Levels in the NHLBI Family Heart Study Arterioscler Thromb Vasc Biol, October 1, 1998; 18(10): 1559 - 1567. [Abstract] [Full Text] [PDF]
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O C E Gebara, M A Mittleman, B W Walsh, I Lipinska, F K Welty, G Bellotti, J E Muller, F K Sacks, and G H Tofler Fibrinolytic potential is significantly increased by oestrogen treatment in postmenopausal women with mild dyslipidaemia Heart, September 1, 1998; 80(3): 235 - 239. [Abstract] [Full Text]
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 R. S. Rosenson and C. C. Tangney Antiatherothrombotic Properties of Statins: Implications for Cardiovascular Event Reduction JAMA, May 27, 1998; 279(20): 1643 - 1650. [Abstract] [Full Text] [PDF]
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A. J. Lee, P. I. Mowbray, G. D.O. Lowe, A. Rumley, F. G. R. Fowkes, and P. L. Allan Blood Viscosity and Elevated Carotid Intima-Media Thickness in Men and Women : The Edinburgh Artery Study Circulation, April 21, 1998; 97(15): 1467 - 1473. [Abstract] [Full Text] [PDF]
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M. Walter, H. Reinecke, G. Breithardt, G. Assmann, J. Heinrich, and P. M. Ridker Factor V Leiden and Thromboembolism • Response Circulation, April 14, 1998; 97(14): 1426 - 1427. [Full Text]
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C. A. DeSouza, P. P. Jones, and D. R. Seals Physical Activity Status and Adverse Age-Related Differences in Coagulation and Fibrinolytic Factors in Women Arterioscler Thromb Vasc Biol, March 1, 1998; 18(3): 362 - 368. [Abstract] [Full Text] [PDF]
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R. W. Nesto and S. Zarich Acute Myocardial Infarction in Diabetes Mellitus : Lessons Learned From ACE Inhibition Circulation, January 13, 1998; 97(1): 12 - 15. [Full Text] [PDF]
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P. Eriksson, L. Nilsson, F. Karpe, and A. Hamsten Very-Low-Density Lipoprotein Response Element in the Promoter Region of the Human Plasminogen Activator Inhibitor-1 Gene Implicated in the Impaired Fibrinolysis of Hypertriglyceridemia Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 20 - 26. [Abstract] [Full Text] [PDF]
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M. Henry, D.A. Tregouet, M.C. Alessi, M.F. Aillaud, S. Visvikis, G. Siest, L. Tiret, and I. Juhan-Vague Metabolic Determinants Are Much More Important Than Genetic Polymorphisms in Determining the PAI-1 Activity and Antigen Plasma Concentrations : A Family Study With Part of the Stanislas Cohort Arterioscler Thromb Vasc Biol, January 1, 1998; 18(1): 84 - 91. [Abstract] [Full Text] [PDF]
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P. Marckmann, E.-M. Bladbjerg, and J. Jespersen Dietary Fish Oil (4 g Daily) and Cardiovascular Risk Markers in Healthy Men Arterioscler Thromb Vasc Biol, December 1, 1997; 17(12): 3384 - 3391. [Abstract] [Full Text]
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M. Frohlich, M. Sund, S. Russ, A. Hoffmeister, H. G. Fischer, V. Hombach, and W. Koenig Seasonal Variations of Rheological and Hemostatic Parameters and Acute-Phase Reactants in Young, Healthy Subjects Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 2692 - 2697. [Abstract] [Full Text]
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P.-Y. Scarabin, M. Alhenc-Gelas, G. Plu-Bureau, P. Taisne, R. Agher, and M. Aiach Effects of Oral and Transdermal Estrogen/Progesterone Regimens on Blood Coagulation and Fibrinolysis in Postmenopausal Women : A Randomized Controlled Trial Arterioscler Thromb Vasc Biol, November 1, 1997; 17(11): 3071 - 3078. [Abstract] [Full Text]
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K. K. Koh, R. Mincemoyer, M. N. Bui, G. Csako, F. Pucino, V. Guetta, M. Waclawiw, and R. O. Cannon Effects of Hormone-Replacement Therapy on Fibrinolysis in Postmenopausal Women N. Engl. J. Med., March 6, 1997; 336(10): 683 - 691. [Abstract] [Full Text] [PDF]
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H. R. Lijnen and D. Collen Impaired Fibrinolysis and the Risk for Coronary Heart Disease Circulation, November 1, 1996; 94(9): 2052 - 2054. [Full Text]
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J. D. Mills, M. W. Mansfield, and P. J. Grant Tissue Plasminogen Activator, Fibrin D-Dimer, and Insulin Resistance in the Relatives of Patients With Premature Coronary Artery Disease Arterioscler Thromb Vasc Biol, April 1, 2002; 22(4): 704 - 709. [Abstract] [Full Text] [PDF]
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